| First Author | Dasgupta SK | Year | 2013 |
| Journal | PLoS One | Volume | 8 |
| Issue | 12 | Pages | e84649 |
| PubMed ID | 24358370 | Mgi Jnum | J:209853 |
| Mgi Id | MGI:5568824 | Doi | 10.1371/journal.pone.0084649 |
| Citation | Dasgupta SK, et al. (2013) Rho associated coiled-coil kinase-1 regulates collagen-induced phosphatidylserine exposure in platelets. PLoS One 8(12):e84649 |
| abstractText | BACKGROUND: The transbilayer movement of phosphatidylserine mediates the platelet procoagulant activity during collagen stimulation. The Rho-associated coiled-coil kinase (ROCK) inhibitor Y-27632 inhibits senescence induced but not activation induced phosphatidylserine exposure. To investigate further the specific mechanisms, we now utilized mice with genetic deletion of the ROCK1 isoform. METHODS AND RESULTS: ROCK1-deficient mouse platelets expose significantly more phosphatidylserine and generate more thrombin upon activation with collagen compared to wild-type platelets. There were no significant defects in platelet shape change, aggregation, or calcium response compared to wild-type platelets. Collagen-stimulated ROCK1-deficient platelets also displayed decreased phosphorylation levels of Lim Kinase-1 and cofilin-1. However, there was no reduction in phosphorylation levels of myosin phosphatase subunit-1 (MYPT1) or myosin light chain (MLC). In an in vivo light/dye-induced endothelial injury/thrombosis model, ROCK1-deficient mice presented a shorter occlusion time in cremasteric venules when compared to wild-type littermates (3.16 +/- 1.33 min versus 6.6 +/- 2.6 min; p = 0.01). CONCLUSIONS: These studies define ROCK1 as a new regulator for collagen-induced phosphatidylserine exposure in platelets with functional consequences on thrombosis. This effect was downstream of calcium signaling and was mediated by Lim Kinase-1 / cofilin-1-induced cytoskeletal changes. |
